Does IM Adrenaline improve survival in OHCA?

Sep 08, 2024

Adrenaline is recommended for all cardiac arrests with non-shockable rhythms and is associated with increased survival, especially if given in the first 10 minutes post arrest (1).

The rate limiting step, which can lead to significant time delays in adrenaline administration, is the establishment of intravenous(IV), or intraosseous(IO) access. Is intramuscular (IM) adrenaline a potential alternative? We already use it for anaphylaxis and in animal models, there is an indication that survival rates may be similar to IV adrenaline (2).

The aim of this study(3) "was to determine whether early IM adrenaline in adult, non-traumatic EMS-treated cardiac arrest is associated with improved survival to hospital discharge."

What They Did

This is a before and after study that looked at the effect of IM adrenaline as an adjunct to current ACLS care. A before and after study measures the outcomes in a group before the intervention and then again after. This was in a single center study, in the...

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Adrenaline is recommended for all cardiac arrests with non-shockable rhythms and is associated with increased survival, especially if given in the first 10 minutes post arrest (1).

The aim of this study(3) "was to determine whether early IM adrenaline in adult, non-traumatic EMS-treated cardiac arrest is associated with improved survival to hospital discharge."

What They Did

Multivariable logistic regression was used to evaluate the association between IM adrenaline and OHCA outcomes.

Patients were included if:

They had continued cardiac arrest after initial shocks for shockable rhythms
If they had non-shockable rhythms and remained in arrest after the first rhythm analysis

Patients were excluded if:

< 18 years of age
They had received adrenaline before first responder arrival
They had a traumatic cardiac arrest,
It was a drowning,
It was a strangulation,
They had return of spontaneous circulation (ROSC) before any adrenaline
There was evidence of irreversible death,
They had a known do-not-resuscitate order.

There were two phases in the study intervention:

The pre-intervention control period
The intervention period:
1. In the control period: patients were treated with IV or IO adrenaline as per standard care.
2. In the intervention period, an IM adrenaline dose of 5 mg was given to the lateral thigh whilst vascular access was being attempted. This was based on the anaphylaxis literature and was equipotent to 0.5mg IV (4)
3. Subsequent adrenaline at 1 mg IV or IO was given every 3–5 minutes, once vascular access was established.

Primary Outcome: survival to hospital discharge.

Secondary Outcomes included:

time from EMS arrival to first adrenaline dose,
survival to hospital admission
survival with a favourable neurologic status at hospital discharge.

Below is an illustration of the selection of the study population(3):

What They Found

The baseline demographics and the time from the emergency call, to first ambulance arrival, were similar in the groups although:

About 26% had an initial shockable rhythm
The IM adrenaline group had a higher rate of bystander CPR
The IM adrenaline group were younger.

Those patients receiving IM adrenaline:

had a better survival to hospital admission (37.1% vs 31.6% OR 1.37)
had a better survival to hospital discharge (11% vs 7% OR 1.73)
had a better functional survival (9.8% vs 6.2% OR 1.72)

Authors' Conclusion

"In this single-center before-and-after implementation study, an initial IM dose of adrenaline as an adjunct to standard ACLS was associated with improved survival to admission, survival to hospital discharge and functional survival."

Limitations of this Study

There were protocol deviations (protocol compliance was 89%) throughout the intervention period.
Before-and-after design could not account for unmeasured and uncontrolled confounders.
There was a small sample size
An optimal IM dose of adrenaline is not known, so an equipotent dose of 0.5 mg IV of adrenaline was given.
This was a single-center, study, limiting its external validity.

My Take on This

This was a study, with many limitations; it was a registry-based study, in a single centre, with multiple protocol violations.

We are unsure if more than one dose of IM adrenaline was given. We aren't sure if the IM adrenaline was the cause of the outcomes. We also are not sure of what effect a 1mg equivalent dose would have.

What we do see with IM adrenaline is a saving in time.The time from ambulance arrival to administration of adrenaline was almost halved in the IM adrenaline group (4.3 minutes vs 7.8 minutes).

The study did not look at time to ROSC, but at time to hospital admission. This was done "due to variations in our EMS agency’s transport practices for patients requiring extracorporeal cardiopulmonary resuscitation"(5)

There are many uncertainties, however it makes us think. What if we could give IM adrenaline to patients in OHCA, or even in hospital arrests, where we don't have IV access and have equivalent outcomes?

We now need a multi-centred randomise controlled trial, to look at IM adrenaline and its effect on survival following cardiac arrest.

POINTS TO TAKE AWAY

This is a before and after study in a single center using from registry data, a small sample and with significant protocol violations
They used IM adrenaline at a 5mg dose (equipotent to 0.5mg IV, as compared to 1mg)
They found that patients given IM adrenaline had a better survival to hospital admission (not ROSC).
It needs an externally validated RCT
Is this something to consider, similar to giving IM adrenaline to anaphylaxis?

References

Ran L, et al. Early administration of adrenaline for out-of-hospital cardiac arrest: a systematic review and meta-analysis. J Am Heart Assoc 2020;9: e014330. https://doi.org/10.1161/JAHA.119.014330.
Mauch J, et al. Intravenous versus intramuscular adrenaline administration during cardiopulmonary resuscitation - a pilot study in piglets. Paediatr Anaesth 2013;23:906–12. https://doi.org/10.1111/pan.12149.
Palatinus H,N et al. Early intramuscular adrenaline administration is associated with improved survival from out-of-hospital cardiac arrest. Resuscitation. 2024 Aug;201:110266. doi: 10.1016/j.resuscitation.2024.110266.
Jacobs IG, et al. Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial. Resuscitation 2011;82:1138–43. https://doi.org/10.1016/j. resuscitation.2011.06.029.
Palatinus H.N et al. Correspondence. Reply to letter: Future thoughts of intramuscular adrenaline in out-of-hospital cardiac arrest resuscitation. Resuscitation 201 (2024) https://doi.org/10.1016/j.resuscitation.2024.110316